Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives

ABSTRACT

Introduction: One-third of breast cancer (BC) cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population.

Areas Covered: We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with BC, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss drugs under development to target the HER2-receptor, and to overcome resistance to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted drugs among older adults.

Expert Opinion: Older adults are underrepresented in trials of HER2-targeted therapies in BC. We propose strategies to increase recruitment of older adults in clinical trials in order to increase the evidence base to treat this growing population.

KEYWORDS:

• HER2 receptor
• breast neoplasms
• molecular targeted therapy
• older adults
• trastuzumab
• lapatinib
• pertuzumab
• cardiotoxicity
• ado-trastuzumab emtansine
• cancer vaccines

Article highlights

• Thirty percent of cases of breast cancer occur in older adults and 10–15% of tumors in older women are epidermal growth factor receptor 2 (HER2) positive

• Older adults are under-represented in clinical trials, and there is a lack of information regarding the efficacy and toxicity of new therapeutic agents in patients who are older, less fit, and/or have more comorbidity.

• In this review, we discuss the current evidence regarding the utilization of various approved and novel HER2-targeted therapies among older adults with breast cancer.

• The efficacy and tolerability of most HER2-targeted therapies among older women seem to be similar to those found in younger women, although this is limited by the small proportion of older adults in clinical trials.

• Studying novel strategies and combinations of targeted treatments is necessary to provide high-quality care, particularly for vulnerable or frail older patients.

This box summarizes the key points contained in the article.

Declaration of Interest

A Hurria reports research funding from Celegene, Novartis, and GSK. Consulting for Boehringer Ingelheim, Carevive, Sanofi, GTx, Pierian Biosciences, and MJH Healthcare Holdings. Yanin Chavarri-Guerra reports research funding from Roche. Tina Hsu has received honoraria from Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This article was not funded.